Changes in purines concentration in the cerebrospinal fluid of patients experiencing pain: A case-control study

Schmidt, André; Böhmer, Ana Elisa; Soares, Félix Alexandre Antunes; Posso, I.P.; Machado, Sheila Braga; Mendes, Florentino Fernandes; Portela, Luis Valmor; Souza, Diogo O.

doi:10.1016/j.neulet.2010.02.067

Cited by 10 publications

(5 citation statements)

References 37 publications

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“…Cut-off and reference ranges were in agreement with those indicated in the literature. Discrepancies in the concentrations of adenosine, inosine and xanthine occurred between our values and those reported by HPLC-UV by Schmidt et al 18 For all three compounds, higher values were reported in our work and in other work, [19][20][21][22][23][24][25] even though no interference or co-elution have been observed in our work. To the best of our knowledge, the present study is the first to report CSF reference concentrations for 2,8-dihydroxyadenine, 5-hydroxymethyluracil, orotic acid, orotidine, pseudouridine, 2-deoxyguanosine, AICAriboside and SAICAR.…”

Section: Purines and Pyrimidines Analysiscontrasting

confidence: 95%

Targeted cerebrospinal fluid analysis for inborn errors of metabolism on an LC‐MS/MS analysis platform

Klinke

Richter

Monostori

et al. 2020

J of Inher Metab Disea

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Background Laboratory investigations of cerebrospinal fluid (CSF) are essential when suspecting an inborn error of metabolism (IEM) involving neurological features. Available tests are currently performed on different analytical platforms, requiring a large sample volume and long turnaround time, which often delays timely diagnosis. Therefore, it would be preferable to have an “one‐instrument” targeted multi‐metabolite approach. Method A liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) platform, based on two different methods for analysing 38 metabolites using positive and negative electrospray ionisation modes, was established. To allow for platform extension, both methods were designed to use the same CSF sample preparation procedure and to be run on the same separation column (ACE C18‐PFP). Results Assessment of the LC‐MS/MS platform methods was first made by analytical validation, followed by the establishment of literature‐based CSF cut‐off values and reference ranges, and by the measurement of available samples obtained from patients with confirmed diagnoses of aromatic l‐amino acid decarboxylase deficiency, guanidinoacetate methyltransferase deficiency, ornithine aminotransferase deficiency, cerebral folate deficiency and methylenetetrahydrofolate reductase deficiency. Conclusion An extendable targeted LC‐MS/MS platform was developed for the analysis of multiple metabolites in CSF, thereby distinguishing samples from patients with IEM from non‐IEM samples. Reference concentrations for several biomarkers in CSF are provided for the first time. By measurement on a single analytical platform, less sample volume is required (200 μL), diagnostic results are obtained faster, and preanalytical issues are reduced. Synopsis LC‐MS/MS platform for CSF analysis consisting of two differentially designed methods.

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Section: Purines and Pyrimidines Analysiscontrasting

confidence: 95%

Targeted cerebrospinal fluid analysis for inborn errors of metabolism on an LC‐MS/MS analysis platform

Klinke

Richter

Monostori

et al. 2020

J of Inher Metab Disea

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“…In vivo human studies have shown higher levels of guanosine in patients suffering from chronic pain and it is correlated with pain severity [ 174 ]. In pregnant women levels of GTP and guanosine are increased in CSF compared to non-pregnant women and acute pain labor is negatively correlated with adenosine levels [ 175 ].…”

Section: Implications Of Guanosine Effects Towards a Clinical Strategmentioning

confidence: 99%

Guanosine: a Neuromodulator with Therapeutic Potential in Brain Disorders

Lanznaster¹,

Dal-Cim²,

Piermartiri³

et al. 2016

Aging and disease

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Guanosine is a purine nucleoside with important functions in cell metabolism and a protective role in response to degenerative diseases or injury. The past decade has seen major advances in identifying the modulatory role of extracellular action of guanosine in the central nervous system (CNS). Evidence from rodent and cell models show a number of neurotrophic and neuroprotective effects of guanosine preventing deleterious consequences of seizures, spinal cord injury, pain, mood disorders and aging-related diseases, such as ischemia, Parkinson’s and Alzheimer’s diseases. The present review describes the findings of in vivo and in vitro studies and offers an update of guanosine effects in the CNS. We address the protein targets for guanosine action and its interaction with glutamatergic and adenosinergic systems and with calcium-activated potassium channels. We also discuss the intracellular mechanisms modulated by guanosine preventing oxidative damage, mitochondrial dysfunction, inflammatory burden and modulation of glutamate transport. New and exciting avenues for future investigation into the protective effects of guanosine include characterization of a selective guanosine receptor. A better understanding of the neuromodulatory action of guanosine will allow the development of therapeutic approach to brain diseases.

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“…The authors suggest that shifts in neuronal and glial energy metabolism might be correlated with pain transmission mechanisms. CSF levels of inosine and other purines associated with ATP metabolism are significantly increased in chronic pain patients compared to control patients and are significantly correlated with pain intensity measured using a visual analog scale ( Schmidt et al, 2010 ). Conversely, serum purine metabolites are increased in fibromyalgia patients (i.e., the dysregulation of pain pathways leading to central sensitization) compared to controls.…”

Section: Inosine and Painmentioning

confidence: 99%

Inosine as a Tool to Understand and Treat Central Nervous System Disorders: A Neglected Actor?

Nascimento

Macedo-Júnior²,

Lapa-Costa

et al. 2021

Front. Neurosci.

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Since the 1970s, when ATP was identified as a co-transmitter in sympathetic and parasympathetic nerves, it and its active metabolite adenosine have been considered relevant signaling molecules in biological and pathological processes in the central nervous system (CNS). Meanwhile, inosine, a naturally occurring purine nucleoside formed by adenosine breakdown, was considered an inert adenosine metabolite and remained a neglected actor on the purinergic signaling scene in the CNS. However, this scenario began to change in the 1980s. In the last four decades, an extensive group of shreds of evidence has supported the importance of mediated effects by inosine in the CNS. Also, inosine was identified as a natural trigger of adenosine receptors. This evidence has shed light on the therapeutic potential of inosine on disease processes involved in neurological and psychiatric disorders. Here, we highlight the clinical and preclinical studies investigating the involvement of inosine in chronic pain, schizophrenia, epilepsy, depression, anxiety, and in neural regeneration and neurodegenerative diseases, such as Parkinson and Alzheimer. Thus, we hope that this review will strengthen the knowledge and stimulate more studies about the effects promoted by inosine in neurological and psychiatric disorders.

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Changes in purines concentration in the cerebrospinal fluid of patients experiencing pain: A case-control study

Cited by 10 publications

References 37 publications

Targeted cerebrospinal fluid analysis for inborn errors of metabolism on an LC‐MS/MS analysis platform

Targeted cerebrospinal fluid analysis for inborn errors of metabolism on an LC‐MS/MS analysis platform

Guanosine: a Neuromodulator with Therapeutic Potential in Brain Disorders

Inosine as a Tool to Understand and Treat Central Nervous System Disorders: A Neglected Actor?

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